1. Field of the Invention
This invention relates to biomedical and orthopedic implants and prostheses and to their use of hydroxyapatite.
2. Description of the Prior Art
Implants and prostheses are commonly used in the medical profession to replace or reinforce diseased or injured hard tissues that are either fractured, damaged, or degenerated. These devices and materials are used, for example, as heart valve replacements, hip implant stems or anchorages, dental implants, knee prostheses, and vertebral spacers. Implants are also used as bone graft substitutes, as alignment maintenance devices in spinal fusion procedures, and as reinforcements for bone weakened by tumor metastases. In some cases, the implants are organs or sections of bone that are transplanted from other portions of the patient's body, while in others, synthetic bones or organs are used. For rigid parts such as bone, fixation is typically achieved by screws, cement, or both. Softer organ and tissue implants are secured by stitching the implants to the surrounding tissues with thread. Still other implants such as breast implants and pacemakers are not securely fixed, but instead rely on natural tissue formation around the implant for securement. In all cases, the success of the implant often depends on its compatibility with, and incorporation into, the biological system, and for those intended for harder tissue, the ability of the implant to form a secure bond to the neighboring healthy tissue. The surface properties of the implant are of primary importance in achieving these goals.
Synthetic materials when used as implants offer certain advantages over transplanted materials in certain applications of this invention. In bone grafts, for instance, the use of a synthetic material rather than a portion of the patient's own iliac crest offers a lower morbidity rate at the donor site and a further advantage for growing children, who have less native bone stock available for use. In spinal fusions, synthetic hydroxyapatite offers an advantage over hydroxyapatite formed by heating coral, since synthetic hydroxyapatite can be manufactured in a less porous and hence stronger form. In cancer patients, bones that have become weakened by tumor metastasis can be replaced or reinforced by a bone graft of synthetic material, again avoiding the need for native bone stock. In other applications of the invention, porosity is desirable. These applications are those where ingrowth of blood vessels and soft tissue are desirable, i.e., those in which the implant is intended to function in a manner comparable to natural bone.
A synthetic material that demonstrates a high level of compatibility with bone and other hard tissue as well as stability in the physiological environment is hydroxyapatite. Hydroxyapatite is a calcium phosphate with the same elemental components as natural bone. Hydroxyapatite is in fact the primary mineral constituent of mammalian bone, constituting 43% by weight of bone composition. The synthetic hydroxyapatite that is used for implants differs from natural bone hydroxyapatite by having fewer impurities and a higher degree of crystallization. Some of the impurities occur as substitutions in the crystal structure. The calcium ions, for example, may be substituted by sodium, potassium, magnesium, lead, manganese, cadmium, strontium, or zinc ions; the hydroxyl sites by halide, oxygen, carbonate, and water; and the phosphate ions by arsenate, sulfate, and carbonate. Deviations from the hydroxyapatite crystal structure form further impurities. These deviations are introduced during synthesis since calcium phosphates can assume many forms and a pure hydroxyapatite material is difficult to synthesize based on the stoichiometric composition. Even though hydroxyapatite is the only calcium phosphate that is stable under normal physiological conditions and other calcium phosphate phases tend to convert to the more stable hydroxyapatite, the transition occurs slowly, allowing the less stable calcium phosphate phases to resorb into the surrounding tissue at rates that vary with their porosity and composition.
Unstable calcium phosphate phases also tend to degenerate into grains which, when released into the body, induce adverse metabolic responses such as a foreign body giant cell response or encapsulation in fibrous tissue. Small particles can also induce an immune response and at times a massive phagocytic cell response. The latter can cause the displacement of normal tissue with a weak, structureless mass of inflamed tissue, leading to the loosening of the implant. Cells that resorb damaged bone (osteoclasts) and those that rebuild bone (osteoblasts) are also affected by the release of small implant particles as the implant deteriorates: small particles tend to activate the osteoclasts and decrease the population of the osteoblasts, the net result being a loss of bone mass.
Other shortcomings of synthetic hydroxyapatite are its flexural strength, strain-to-failure ratio, and fracture toughness, all of which are low relative to bone. Synthetic hydroxyapatite is thus relatively brittle and has low fatigue resistance, and for these reasons is not used in load-bearing locations.
Various methods have been used in the prior art for modifying hydroxyapatite and other implant materials to improve their bone adhesion and other properties. Among these methods are the use of bone morphogenetic proteins as a coating on the implant surface to improve cell adhesion and subsequent tissue attachment. Methods of applying these coatings and their effects are reported in references cited by Zeng, H., et al., Biomaterials 20 (1999): 377–384. To improve the hardness of the implant material and its chemical inertia to the biological environment, nitrogen atoms have been introduced into the material by nitridation. This has been reported for both hydroxyapatite and titanium implants by Habelitz, S., et al., J. European Ceramic Society 19 (1999): 2685–2694, and Torrisi, L., Metallurgical Science and Technology 17(1) (1999): 27–32.